Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
  • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
  • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D213/72—Nitrogen atoms
  • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals

Definitions

• This invention relates generally to polymer-supported catalysts having pyridylamino functionality, and in particular to a cross-linked copolymer of vinyl substituted 4 (N benzyl-N methylamino)pyridine and a styrene monomer derivative characterized by improved physical properties and marked catalytic activity, and to the process for preparing the same.
• DMAP dimethylaminopyridine
• certain of its dialkylamino analogs are highly effective catalysts for acylations, alkylations and other related reactions.
• Also recognized for some time has been the desirability of a polymer bound or supported version of such DMAP like catalysts in view of the potential advantages of ease of recovery and repeated use along with the adaptability of such catalysts in both static and flow systems.
• insoluble, heterogeneous gel or macroreticular resin beads provide the greater advantages in ease of removal and recyclability.
• Verducci and his coworkers reported attaching 4-piperidinylpyridine, among other DMAP like moieties, to a Merrifield resin also through an amide bond. Guendouz, F., Jacquier, R., Verducci, J., Tetrahedon Lett., 25, 4521 (1984). The amide bond 1n this polymer, however, was reported to stand up well on recycle in the catalytic acetylation of 1-methylcyclohexanol at 70° C. and 24 hours.
• Tomoi Another group of investigators led by Tomoi has compared two other approaches to achieve a similar polymeric BMAP catalyst. Tomoi, M., Akada, Y., Kakiuchi, H., Macromol. Chem.. Rapid Commun., 3, 537 (1982). Tomoi reported, among other things, that a route involving copolymerization of the preformed BMAP monomer gave a better catalyst product. However, more recently a group led by Frechet challenged this conclusion, reporting that preformed chloromethylated polystyrene can be modified readily and quantitatively to produce an even better catalyst. Frechet, J.M.J., Deratini, A., Darling, G, Lecavalier, P., Li, N.H., Macromol.
• these polymers prepared according to the literature references contain significant amounts of granular powders, flake or other irregular shapes instead of the predominant bead form that is preferred. Such unwanted particles are mechanically unstable and suitable for use only in stirred-slurry or other reactors where clogging of filters or lines is not a concern and where recycling of the catalyst is not contemplated.
• the gel type bead segments that are present in these reference materials are nonuniform in size or configuration, exhibit great deviation from the average or median size present, and do not show the durable, hard form that is preferred.
• Frechet has reported making a 34% divinylbenzene (DVB) cross linked macroreticular resin also within this class, he reported and subsequent testing has confirmed that it has inferior chemical and physical properties as a catalyst in the acylation of 1-methylcyclohexanol.
• Frechet's resin made from his preferred chloromethylated polystyrene process may contain quaternary salt from unwanted side reactions which can react to ring-open under strongly basic conditions as often encountered.
• This polymeric BMAP catalyst is prepared through the free radical suspension copolymerization of an organic phase comprIsing the vinyl-substituted BMAP monomer, a styrene monomer and a suitable free radical-generating catalyst and cross-linking agent in the presence of a selected aqueous suspending medium.
• this polymer supported BMAP material is characterized by its generally spherical and smooth bead form and substantially uniform size ranging up to about 1.0 mm in diameter and exhibiting minimal deviation from the median or average bead size in a given batch.
• the beads are hard and durable, being both easily recoverable following copolymerization and readily recyclable in use.
• the beads may have a gel or a macroreticular structure, as desired, depending upon the degree of cross linking and other factors such as the presence of a suitable diluent such as an organic solvent in the copolymerization process
• the beads are also characterized by the absence of any significant amount of granular powders, flake or other irregular particles either as originally formed or as the result of unwanted deterioration from normal catalytic use.
• the beads have further shown to have highly effective catalytic activity approaching that of DMAP in the reactions tested.
• the applicants have discovered a commercially significant DMAP-like polymer resin containing 4 methylaminopyridine groups functionally bound to a cross-linked styrene backbone at the 4-amino site through a vinylbenzyl linkage.
• the preparative process of choice comprises the suspension copolymerization of vinyl substituted 4-(N benzyl N-methylamino)pyridine with a styrene monomer and a suitable cross-linking agent and free radical generating catalyst. This is contrasted by the indirect method reported in the literature which involves subsequently attaching 4-pyridineamine groups to a preformed chloromethylated polystyrene resin.
• free radical suspension copolymerization are well known to those skilled in this art and comprise the process of polymerizing a comonomer mixture which has been suspended in the form of droplets in a medium of some composition in which the monomers are at least substantially insoluble.
• the discrete nature of these droplets and the size and stability of the suspension depend in large part on the nature of the medium used including its individual components or additives, as well as on various physical factors in the procedure such as stirring rate, temperature and the like.
• the medium used in this invention is an aqueous phase suspension of a particular class of stabilizing agent as described below.
• these droplets appear and take on various forms which will affect their physical and chemical properties in later use. Although it is common to refer to all such polymer droplets as "beads,” in fact they may range from granular powders, flake or other irregular shaped particles such as produced by the prior art processes discussed above to the predominantly uniform and smooth, hard spherical beads achieved by the applicant's invention.
• One method of promoting the copolymerization is to provide a suitable catalyst which when elevated to a sufficient temperature will decompose to provide free radicals which function as initiators for the reaction.
• Two general classes of such free radical generating catalysts are known, those being peroxides and azo compounds.
• the selection of an initiator within these groups, and its amount and method of use, is within the knowledge and skill of the art and depends on availability, on the specific comonomer mixture used and on other factors affecting the reaction.
• the catalyst used in the applicants' work has been an azo compound identified as 2,2'-azobis-(2,4 dimethylvaleronitrile) and marketed by E. I. du Pont de Nemours & Company (DuPont) under the trademark Vazo 52.
• the preferred range of this catalyst has been from about 0.1-1.0% by weight of the total comonomer components used. It is nonetheless understood that other catalysts within these groups are similarly suited for this purpose and are within the scope of the invention.
• a suitable cross linking agent must also be included in the organic component during the copolymerization process.
• Many such cross linking agents are commercially available, and their utility and interchangeability in reactions such as the process at hand are well known to those skilled in this art.
• the applicants have to date used a commercial divinylbenzene (commonly referred to as "DVB") for this purpose in amounts varying according to the desired physical structure of the reaction product as further discussed below.
• DVD commercial divinylbenzene
• reaction conditions for the preferred process such as the temperatures and times for the copolymerization to occur as well as appropriate equipment and procedures such as the desirability of agitation and the like are also well known to those practiced in this art. Accordingly, the same require little further elaboration in this specification.
• the temperature to initiate polymerization depends as a practical limit on the decomposition temperature of the free radical-generating catalyst used. As some reactions in this class are exothermic, little or no additional heating is necessary although some may be desirable at later stages to assure complete copolymerization of the monomer present.
• an initiation temperature of about 55° C. was employed with an elevated temperature of about 85° C. used to finish off the reaction.
• this initiation temperature may increase or decrease significantly coupled with completing the reaction at temperatures up to or at reflux of about 100° C. or above. It is similarly known, for example, that oxygen inhibits these reactions and was therefore kept from the system in the Examples below by maintaining a nitrogen purge during the copolymerization process.
• the cross linked polymer supported BMAP material in accordance with the invention is characterized by being suspension copolymerized in the presence of a particular aqueous phase which comprises a cellulose ether derivative as the stabilizing or suspending agent.
• Suitable cellulose ether derivatives include methylcellulose (such as Methocel A from Dow Chemical Corporation of Midland, Michigan and Culminal from Aqualon Company of Wilmington, Delaware); hydroxyethylcellulose (such as Natrosol 250 from Aqualon and Cellosize from Union Carbide Corporation of Danbury, Connecticut); hydroxypropylcellulose (such as Klucel J from Aqualon); hydroxypropyl methylcellulose (such as Methocel E, F, J and K and 50 123 from Dow Chemical and Culminal MHPC from Aqualon); hydroxyethyl methylcellulose (such as Culminal from Aqualon); carboxymethyl methylcellulose (such as CMMC from Aqualon); hydrophobically-modified hydroxyethylcellulose (such as HMHEC WSP-M 1017 from Aqualon); carboxymethyl hydroxyethylcellulose (such as CMHEC 37L from Aqualon); and hydroxypropyl hydroxyethylcellulose (
• this stabilizing additive in the aqueous phase will vary according to the cellulose ether used as well as other factors. From work thus far some preference has been shown for hydroxypropyl methylcellulose (such as Methocel 50 123 from Dow Chemical), hydrophobically modified hydroxyethylcellulose (such as HMHEC WSP M 1017 from Aqualon) and carboxymethyl hydroxyethylcellulose (such a CMHEC 37L from Aqualon) in preferred concentrations up to about one-half percent (0.50%) by weight of the total aqueous phase. Most preferred have been concentrations of about one tenth percent (0.10%) by weight.
• hydroxypropyl methylcellulose such as Methocel 50 123 from Dow Chemical
• hydrophobically modified hydroxyethylcellulose such as HMHEC WSP M 1017 from Aqualon
• carboxymethyl hydroxyethylcellulose such a CMHEC 37L from Aqualon
• the selection of materials for the organic monomer phase in accordance with the invention first involves preparing the vinyl substituted 4(N-benzyl N-methylamino)pyridine (BMAP) monomer through the reaction of 4-(N-methylamino)pyridine with vinylbenzylchloride as reported in the 1982 Tomoi article previously referenced. Also present is a styrene monomer component including styrene itself and/or substituted styrene derivative such as ethylstyrene which is similarly suited for this purpose and is within the scope of the invention. Still further, there is a suitable free radical generating catalyst and cross linking agent in accordance with the descriptions above.
• BMAP loading is a convenient measure as the amount of pyridylamino groups present has a direct relationship to the functioning of the copolymer resin as a catalyst in acylation, alkylation or other related reactions.
• the preferred polymer supported material has been successfully prepared in accordance with the invention across a wide range of BMAP loading up to about 50% by weight of the BMAP monomer compared to the total monomer present in the organic phase. This is approximately equivalent to a mole percent up to about 33% and to molar ratio up to about 1:2 of BMAP monomer to total styrenic monomer in the organic phase.
• total styrenic monomer is meant to include styrene and any styrene derivatives such as ethylstyrene and divinylbenzene, and is in deference to the fact that commercial DVB cross-linking agent is a styrene derivative having some unreacted ethylstyrene component.
• commercial DVB cross-linking agent is a styrene derivative having some unreacted ethylstyrene component.
• the 55% DVB used in the Examples below typically has about 45% ethylstyren remaining in the material. This entire DVB component including the extraneous styrenic material is included in the BMAP loading calculation.
• the most preferred BMAP loading from work performed to date is about 34% by weight of BMAP monomer compared to total styrenic monomer in the organic phase, which equates to about 20 mole percent and to a molar ratio of about 1:4.
• the amount of agent such as divinylbenzene in the organic monomer phase directly affects the degree of cross linking and to a large extent both the physical and chemical properties of the resulting copolymer catalyst product.
• decreasing concentrations of DVB below about 8-10% by weight in accordance with the invention has produced effective gel resins that are generally translucent and hard, durable beads in appearance and exhibit increasing swellability and accompanying activity typical of lower degrees of cross linking.
• Increasing concentrations of DVB above about 8-10% by weight has produced similarly effective gel resins that are general harder bead forms less subJect to swelling or disintegration during use and exhibit some possible loss of accompanying activity typical of such higher degrees of cross linking.
• the resulting product has been effectively changed from a gel to a macroreticular bead form as determined by the presence of a permanent pore structure and opaque appearance typical of such resins upon later removal of the solvent.
• a suitable diluent such as an organic solvent
• the applicants have employed a VMP Naphtha material distributed by Chem Central of Indianapolis, Indiana in about 33% by weight of the total organic phase.
• the applicants' preferred polymeric material has shown effective catalytic properties at 15% cross-linking in both gel and macroreticular forms. Selection of the appropriate cross linking and resin form for a given catalytic reaction, including the nature and amount of any solvent used, is well within the knowledge and skill of those practiced in this art and is within the scope of the present invention.
• the cross-linked polymer-supported BMAP material of the invention is further characterized and distinguished from the art by the same physical and catalytic properties which have been surprisingly discovered.
• the preferred copolymer material has been prepared in high yield well in excess of 90% of the total recovered product. More importantly, the preferred material has shown little or no evidence of clumping or of the presence of granular powders, flake or other irregular material to hamper later use or recycling of the catalyst. On the contrary, the preferred material has exhibited a generally smooth and spherical bead form with the further advantage of a substantially uniform size distribution ranging up to about 1.0 mm in diameter and a minimal deviation from the median or average bead size in a given reaction.
• An aqueous phase was first prepared using water and one of the cellulose ether derivatives listed in Example 2, as the stabilizing or suspending agent. 150ml of this aqueous phase was added to a 300 ml roundbottom flask fitted with a condenser, nitrogen purge ports, a thermometer and a stirrer equipped with a glass stirring shaft and Teflon blade. The aqueous solution was purged with nitrogen, stirred and brought to the appropriate reaction temperature to permit free radical generation by the catalyst being used (with Vazo 52, this was about 55° C.). Approximately 30 g of one of the organic monomer phases also listed in Example 2 was then added to the stirred aqueous phase below the liquid surface through a long-necked funnel.
• the resulting dispersion was maintained at the reaction temperature (about 55.C.) with continued stirring and nitrogen purge for 3 hours until the copolymerization was substantially complete.
• the dispersion was then heated to about 85° C. and maintained at that temperature for 16 hours with continued stirring and nitrogen purge to finish off the reaction, followed by cooling to room temperature.
• the insoluble cross-linked polymex supported BMAP resin beads were removed from the remaining liquid by filtration, rinsed and dried, then their identification and composition confirmed through infrared (I.R.) and elemental combustion analysis.
• aqueous phase solutions were prepared in accordance with the invention using each of the cellulose ether derivatives previously identified in the specification as the stabilizing or suspending agent.
• methylcellulose such as Methocel A from Dow Chemical Corporation of Midland, Michigan and Culminal from Aqualon Company of Wilmington, Delaware
• hydroxyethylcellulose such as Natrosol 250 from Aqualon and Cellosize from Union Carbide Corporation of Danbury, Connecticut
• hydroxypropylcellulose such as Klucel J from Aqualon
• hydroxypropyl methylcellulose such as Methocel E, F, J and K and 50-123 from Dow Chemical and Culminal MHPC from Aqualon
• hydroxyethyl methylcellulose such as Culminal from Aqualon
• carboxymethyl methylcellulose such as CMMC from Aqualon
• hydrophobically-modified hydroxyethylcellulose such as HMHEC WSP-M 1017 from Aqualon carboxymethyl hydroxyethylcellulose
• approximately 30 g of organic phase at 2% cross linking and 34% BMAP loading contained 11.2 g BMAP monomer, 1.18 g 55% DVB, 19.88 g styrene and 0.16 g Vazo 52.
• a similarly 4% cross linked material at 15% BMAP loading contained 3.73 g BMAP monomer, 1.82 g DVB, 18.93 g styrene and 0.12 g Vazo 52, at 20% BMAP loading contained 8.26 g BMAP monomer, 2.74 g DVB, 29.14 g styrene and 0.16 g Vazo 52, and at 50% BMAP loading contained 15.00 g BMAP monomer, 2.20 g DVB, 13.91 g styrene and 0.16 g Vazo 52.
• organic phase at 4% cross linking and 34% BMAP loading contained 11.2 g BMAP monomer, 2.37 g 55% DVB, 18.94 g styrene and 0.16 g Vazo 52.
• Still further organic phases were prepared at these three levels of BMAP loading with varying amounts of DVB to prepare copolymer products at levels of cross linking increasing by 2% up to 12% by weight of the organic phase.
• additional mixtures were prepared according to known procedures, but simply with stoichiometrically varying amounts of individual components to arrive at the concentrations desired.
• Example 2 Employing the suspension copolymerization procedure of Example 1 and the aqueous and organic phases of Example 2, the applicants prepared, isolated and identified by I.R. and elemental combustion analysis the polymer supported BMAP materials obtained from these reactions in accordance with the present invention.
• the copolymer yield was well in excess of 90% by weight of the total reactants and was characterized by a predominant and generally smooth and spherical bead form and substantially uniform size ranging from up to about 1.0 mm in diameter with a minimal deviation in bead size in each yield.
• Each copolymer product was further characterized by the absence of clumping or any significant extraneous material such as the granular powders, flake and other irregular-shaped particles common to literature preparations.
• each product was hard, durable and generally translucent giving the overall appearance of an effective gel resin for catalytic purposes.
• Microscopic examination of the copolymers showed no fractures or bubbles in the particle beads as formed.
• no significant fracturing of the recovered beads was found thereby confirming their durability and recyclability in a commercial setting.
• the stabilizing additives most preferred have been Methocel 50-123, HMHEC and CMHEC 37L as previously described.
• the polymer-supported BMAP resins most preferred have similarly possessed a 34% BMAP loading with either 2% or 4% cross-linking.
• Two organic monomer mixtures were prepared using the following recipes: For the gel resin, 10.20 g BMAP monomer (as used in Example 2), 11.62 g styrene, 8.18 g 55% DVB and 0.15 g Vazo 52 were combined with stirring to give a homogeneous solution which was maintained at about 5° C. until its addition to the aqueous phase during copolymerization. For the macroreticular resin, the same procedure was followed using 10.2 g BMAP monomer, 11.62 g styrene; 8.18 g 55% DVB, 9.90 g VMP Naphtha and 0.16 g Vazo 52.
• Example 1 The suspension copolymerization of each monomer phase was then carried out according to the procedure of Example 1. Confirmation of each copolymer composition was by I.R. and elemental combustion analysis.
• the gel resin appeared as translucent, generally spherical and smooth beads that were consistent with the overall physical properties of the other material described in the specification in accordance with the invention.
• the macroreticular resin similarly appeared as generally spherical and smooth bead particles also of a substantially uniform size and appearance, but with a whitish color consistent with the presence of substantial microporous channels throughout the bead structure characteristic of such materials. Porosity was confirmed by surface area measurements (ca. 30 m 2 /g). Both polymer resins proved hard and durable when used in the following reactions and were then recovered for recycling in each case after washing with appropriate solvents to displace any residual water present.
• Suspension copolymerizations were carried out in the manner described as follows comparing one of the preferred aqueous phases in the invention using Methocel 50-123 as the stabilizing additive against the aqueous phases reported by groups led by Tomoi (Tomoi, M., and Ford, W.T., J. Am. Chem.
• the Tomoi aqueous phase was prepared by mixing a solution containing 1.35 g gelatin, 12.5 g Merquat 100 (which is poly(diallyldimethylammonium chloride) marketed by Calgon Corp., Pittsburg, Pennsylvania) and 5.1 g boric acid in 450 g of water. Its pH was adJusted to 10.0 with a 25% aqueous solution of sodium hydroxide.
• the Frechet aqueous phase was prepared by simply dissolving 6.75 g polyvinylalcohol (Airvol 523 manufactured by Air Products and Chemicals, Inc. of Allentown, Pennsylvania) in 450 g of water.
• aqueous phase in accordance with the present invention which was in this test was prepared as described in Example 4.
• the cross linked copolymers prepared using the Tomoi aqueous phase and both organic phases yielded particles that were not uniformly spherical and varied greatly in size.
• the products contained a significant amount of flake and fine powders, making it very difficult to filter or recover from any commercial process.
• the distorted beads showed visible signs of fractures under microscopic analysis and readily broke into smaller fragments upon swelling and recapture from a toluene solvent. Similarly, severe fracturing was noted when a slurry of this material in toluene was stirred for several hours.
• cross linked copolymers prepared using the Frechet aqueous phase and both organic phases consisted substantially of clumps of small distorted bead forms. Attempts to separate these particles resulted in substantial fracture of the discernable beads present in the material. Microscopic examination of these bead clumps revealed both fractures and many tiny bubbles and other imperfections in the particles. Similar to the Tomoi material, these copolymers also broke into smaller fragments upon repeated swelling in toluene and upon stirring in a slurry for several hours.
• the cross-linked copolymers prepared using the aqueous phase of the present invention produced materials in yields over 90% by weight consisting primarily of smooth spherical beads that were hard and translucent giving all appearances of a superior gel resin structure.
• the beads were substantially uniform in size with minimal deviation of about 10% from the median or average bead size in each case. Little or no extraneous irregular shaped material was produced, and microscopic examination showed no signs of fractures or bubbles in the produced particles.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Pyridine Compounds (AREA)
• Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
• Catalysts (AREA)
• Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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